Partition coefficient basic drugs

Bard, B., Carrupt, P.A. and Martel, S. (2009) Determination of partition coefficients of basic drugs using hydrophilic interaction chromatography. Journal of Medicinal Chemistry, 52, 3416-3419. 

C. Lead can substitute for calcium in the bone crystal lattice, resulting in bone brittleness. Bone may become a reservoir for other substances as well. Several drugs, such as chlorpromazine, may accumulate in the eye. Drugs with extremely high Upid-water partition coefficients tend to accumulate in fat, while basic amines tend to accumulate in the lungs. Many agents bind avidly to albumin in the blood. 

Tab. 4.26 Tissue-to-plasma partition coefficients (Kp) of basic drugs for various rabbit tissues , octanol-buffer partition coefficient, log Papp, and unbound fraction of drug in serum, fp (Adapted from Tab. 2 of ref. 91)...

Since passive diffusion is the primary driving force behind dermal absorption, physicochemical factors such as molecular weight and structure, lipophilicity, pKa, ionization, solubility, partition coefficients, and diffusivity can influence the dermal absorption of various classes of chemicals. In addition penetration of acidic and basic compounds will be influenced by the skin surface, which is weakly acidic (pH 4.2-5.6), since only the uncharged moiety of weak acids and bases is capable of diffusing though the lipid pathway. Several of these factors (e.g., molecular weight, and partition coefficients) have been used to predict absorption of various drug classes [24-26],... 

Seiler P, Simultaneous determination of partition coefficient and acidity constant of a substance, Eur. J. Med. Chem., 9, 663-665 (1974). Cited in Lombardo F, Obach RS, Shalaeva MY and Gao F, Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics, /. Med. Chem., 47, 1242-1250 (2004) (ref. 279). NB Titrations were performed by autotitrator in the presence of hi purity dodecane, to allow simultaneous measurement of the log P value. The pH meter was calibrated against three standard solutions. 

Rodgers et al. (2005,2007) and Rodgers and Rowland (2006,2007) incorporated drug ionization and the interaction of strong bases with acidic phospholipids in calculating partition coefficients (K ) for dmgs, where Kp = Kp x / . The basic equation for the calculation of unbound tissue-plasma partition coefficient, Kp, is shown in (24) as it has been rewritten by Simulations-Plus, Inc., Lancaster, CA in their GastroPlus user manual (version 6.0). 

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